Modulation of chemoimmunotherapy efficacy in non-small cell lung cancer by sex and histology: A real-world, patient-level analysis

It has been postulated that patient’s sex impacts response to immunotherapy. Sex modulation of immunotherapy benefit, however, has not yet been explored using patient-level data, where potential confounder, as well as histologic type, can be accounted for. Here we investigated the association between sex and chemoimmunotherapy efficacy for non-small cell lung cancer (NSCLC) using a large, nation-wide dataset.
Nội dung trích xuất từ tài liệu:
Modulation of chemoimmunotherapy efficacy in non-small cell lung cancer by sex and histology: A real-world, patient-level analysisTuminelloetal. BMC Cancer (2022) 22:80https://doi.org/10.1186/s12885-022-09187-y RESEARCH Open AccessModulation ofchemoimmunotherapyefficacy innon-small cell lung cancer bysexandhistology: areal-world, patient-levelanalysisStephanieTuminello1,2, NaomiAlpert1, RajwanthR.Veluswamy1,3,4, ArvindKumar4, JorgeE.Gomez4,RajaFlores5and EmanuelaTaioli1,4,6*  Abstract  Background:  It has been postulated that patient’s sex impacts response to immunotherapy. Sex modulation of immunotherapy benefit, however, has not yet been explored using patient-level data, where potential confounders, as well as histologic type, can be accounted for. Here we investigated the association between sex and chemoimmu- notherapy efficacy for non-small cell lung cancer (NSCLC) using a large, nation-wide dataset. Patients & methods:  Stage IV NSCLC patients diagnosed in 2015 were identified in the National Cancer Database (NCDB). Patients were treated with either chemoimmunotherapy or chemotherapy alone. The efficacy of the addition of immunotherapy treatment by sex was investigated using both an adjusted Cox proportional hazards model and propensity-score matching, in both the overall cohort and stratified by histological subtype. Results:  2064 (16%) patients received chemoimmunotherapy and10,733 (84%) received chemotherapy alone. Adjusted survival analysis in the overall cohort showed that both males (hazards ratio (HR)adj: 0.80, 95% CI: 0.74–0.87) and females (HRadj: 0.83, 95% CI: 0.76–0.90) had better OS when treated with chemoimmunotherapy than chemo- therapy alone, with no statistically significant interaction between sex and receipt of immunotherapy (p = 0.63). Propensity matching confirmed these results. However, for those with squamous cell histology, male patients derived more benefit from chemoimmunotherapy treatment than females (HRadj: 0.73, 95% CI: 0.58–0.91 vs HRadj: 1.03, 95% CI: 0.76–1.38; p for interaction = 0.07). Conclusion:  Male patients with squamous cell carcinoma may derive more benefit from chemoimmunotherapy treatment. Histology likely plays an important role in how sex modulates immunotherapy efficacy. Keywords:  Immunotherapy, NSCLC, Immune checkpoint inhibitors, Squamous cell carcinoma Introduction Platinum-based doublet chemotherapy was the main- stay treatment for advanced, non-small cell lung cancer (NSCLC) for decades, until, in 2015, the FDA approved Pembrolizumab for patients with metastatic disease*Correspondence: Emanuela.taioli@mountsinai.org who had: 1) failed to respond to other treatments and4 Tisch Cancer Institute, Icahn School ofMedicine atMount Sinai, New 2) had tumors expressing PD-L1 [1]. Immune check-York, NY, USAFull list of author information is available at the end of the article point inhibitors (either anti-CTLA-4 or anti-PD-1/PD-L © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/. The Creative Commons Public Domain Dedication waiver (http://​creat​iveco​ ...